Evidence for the presence of D2 and 5-HT2 receptors in the human prefrontal cortex.

Abstract

The D2 receptor and two distinct affinity 5-HT2 receptors in the human prefrontal cortex were labeled with 3H-spiperone. In the Scatchard analysis of stereoselective binding defined by (+)- and (-)-butaclamol, two high affinity binding sites were clearly demonstrated. Apparent KD values of these higher and lower affinity sites determined in this manner were 0.028 and 0.64 nM, respectively. However, drug displacement studies of 3H-spiperone binding at these sites, using different concentrations of 3H-spiperone (0.05 nM for higher affinity sites and 0.5 nM for lower affinity sites), indicated that 70-80% of the higher affinity sites and almost all of the lower affinity sites showed characteristics of the 5-HT2 receptor and that 20-30% of the higher affinity sites showed characteristics of the D2 dopamine receptor. An additional saturation experiment related to the specific binding of 3H-spiperone to 5-HT2 receptors confirmed the existence of two distinct populations of 5-HT2 receptors that had different affinities for spiperone. Apparent KD values for higher and lower affinity 5-HT2 receptors were 0.091 and 1.27 nM, respectively. As the D2 receptor is a possible site of antipsychotic action of neuroleptics, these receptors, especially the D2 receptor in the human prefrontal cortex, seem to play an important role in psychotic disorders.